1,3-Diaxially Substituted trans-Decalins: Potential Nonsteroidal Human Progesterone Receptor Inhibitors

On the basis of molecular modeling and QSAR analysis of the known human progesterone receptor (hPR) inhibitor Mifepristone (RU-486) and other hPR ligands, a new class of potential nonsteroidal hPR inhibitors was designed. The parent racemic compound 1 was synthesized through an efficient 13-step synthetic pathway. The key constructive steps are a stereoselective epoxide ring opening and the reductive Heck cyclization to form the main framework of (±)-1. The current established flexible synthetic route allows for further chemical diversification.